Storage-stable compositions of glycerol monoalkyl ethers

ABSTRACT

The present invention relates to compositions which comprise a combination  
     a) of one or more glycerol monoalkyl ether(s) of the general formula  
     R—O—CH 2 —CHOH—CH 2 OH  
     in which R is a branched or unbranched C 3 -C 18 -alkyl group, where the alkyl group can be substituted by one or more hydroxyl and/or C 1 -C 4 -alkoxy group(s) and/or the alkyl chain can be interrupted by up to four oxygen atoms, with  
     b) an antioxidant or two or more antioxidants as stabilizer(s),  
     the simultaneous presence of phosphocholines and phosphocholine derivatives being excluded.

[0001] The present invention relates to compositions comprising glycerolmonoalkyl ethers for use in cosmetic and pharmaceutical preparations andin technical products. These compositions have in particular goodlong-term storage stability and comprise at least one glycerol monoalkylether and at least one antioxidant as stabilizer.

[0002] Of the two substitution-isomeric glycerol monoalkyl ethers(2-alkoxy-1,3-propanediols and 3-alkoxy-1,2-propanediols), the presentinvention relates in particular to the 3-alkoxy-1,2-propanediols.

[0003] The invention further relates to concentrates and workingsolutions. The compositions according to the invention, i.e. inparticular the concentrates and working solutions, are added topharmaceutical and cosmetic preparations and technical products.

[0004] Glycerol monoalkyl ethers are used as additives for cosmetic andpharmaceutical preparations and have a multifaceted action. Thus, forexample, they are used as physiologically compatible organic solvents.In particular, 3-[(2-ethylhexyl)oxy]-1,2-propanediol (Sensiva® SC 50)has been used increasingly for some years as a deodorant activeingredient and skin care additive in cosmetic and pharmaceuticalpreparations. Here, the glycerol monoalkyl ethers are added to thepreparations or technical products usually in the form of a concentrateor as a pure glycerol monoalkyl ether.

[0005] During manufacture, storage and use, the glycerol monoalkylether, its concentrate and its dilute solution (working solution) aresubject to high requirements which arise from the increased demands ofthe consumer on the quality of cosmetic and pharmaceutical preparations.

[0006] The glycerol monoalkyl ethers are largely chemically stable andstable to external atmospheric influences. They are often colourless,almost odourless liquids and, because of their good chemical stability,are highly compatible with most cosmetic and pharmaceutical ingredients.Because glycerol monoalkyl ethers occur naturally, even thesynthetically prepared representatives of the class of substance areparticularly desirable for use in end-products because they are widelyaccepted by manufacturers of cosmetics and pharmaceuticals and endusers.

[0007] DE 41 40 474 A1 describes the use of certain glycerol monoalkylethers in particular as skin care additive for products from thecosmetic and pharmaceutical and quasicosmetic sector and emphasizestheir high chemical stability.

[0008] EP 0 599 433 A1 discloses that glycerol monoalkyl ethers exhibiteffectiveness against odour-causing Gram-positive bacteria. In thisconnection, deodorizing glycerol monoalkyl ethers of a specificallylow-odour and low-peroxide quality are particularly preferred.

[0009] EP 0 593 897 A1 discloses aqueous phosphocholine preparations inwhich glycerol monoalkyl ethers, i.e. 3-alkoxy-1,2-propanediols and2-alkoxy-1,3-propanediols, are used as physiologically compatibleorganic solvents. The pharmaceutical preparations disclosed therein arenot storage-stable even in the presence of antioxidants. In EP 0 593 897A1, the stability is improved by the addition of a buffer.

[0010] We have now found that the storage stability, in particular thelong-term storage stability (over several months to years), with regardto the peroxide content of preparations comprising glycerol monoalkylethers is unsatisfactory. Thus, for example, manufacturers of cosmeticscomplain that incompatibilities between glycerol monoalkyl ethers andformulation constituents or changes in quality of the end-products havebeen established. The cause of these losses in quality may inter alia bea formation of peroxide which takes place in the preparations dependingon the time and storage. The peroxide content in stored preparationsvaries comparatively greatly and cannot be calculated (chaoticdevelopment of the peroxide number, see Experiments A and A (Alu) inTable 1 in Example 1). Furthermore, the appearance of undesireddegradation products of low molecular weight was detected by chemicalanalysis.

[0011] The disadvantages of traditional preparations comprising glycerolmonoalkyl ethers arise in concentrated and dilute glycerol monoalkylether solutions or finished products and can be summarized as follows:

[0012] 1. Peroxides in cosmetic and pharmaceutical preparations, inparticular skin care compositions, when used on the skin of persons witha predisposition, trigger the clinical picture of Mallorca acne (a lightdermatosis).

[0013] 2. A change in the odour of stored precursors or products orstored glycerol monoalkyl ethers results.

[0014] 3. A change in the odour of cosmetic products as a result ofoxidation of natural fats and oils present therein results.

[0015] 4. Greying of oil-in-water emulsions comprising glycerolmonoalkyl ethers arises as a result of incompatibilities of storedmixtures with ingredients of cosmetics and pharmaceuticals.

[0016] 5. Degradation products of low molecular weight can be detectedby chemical analysis.

[0017] 6. The abovementioned disadvantages can lead to toxicologicalexpert opinions which have a tendency to be relatively unfavourable forcosmetics and pharmaceuticals which have been prepared using storedglycerol monoalkyl ethers.

[0018] 7. The mixtures, e.g. glycerol monoalkyl ether concentrates, areusually stored in plastic containers. During storage, permanentdeformations of plastic containers have been observed, which is referredto as the neck-in effect. Containers with a severe neck-in effect can nolonger be stacked safely.

[0019] 8. Regular quality control of stored glycerol monoalkyl ethers bythe cosmetics and pharmaceuticals manufacturers is technologicallylaborious, long-term storage of glycerol monoalkyl ethers cannot alwaysbe avoided and the disposal of amounts of glycerol monoalkyl etherswhich have become unusable causes additional costs.

[0020] Accordingly, the object of the present invention is to providecompositions which comprise one or more glycerol monoalkyl ethers, theintention being for these compositions to be storage-stable, inparticular storage-stable for a long period, and be storable and stableunder practical conditions. Preferably, the abovementioned disadvantagesshould not arise during storage up to 60 months, more preferably 12 to36 months, e.g. 12 months or 24 months. A further object of the presentinvention is to provide stabilizers which can be used for the long-termstabilization of glycerol monoalkyl ethers. These stabilizers should,added in a low mixing ratio to glycerol monoalkyl ethers or preparationscomprising glycerol monoalkyl ethers, protect these preparations fromdecomposition, in particular with the development of high peroxidenumbers.

[0021] These objects are achieved by the present invention. According toPatent Claim 1, the stable composition is characterized in that itcomprises a combination

[0022] a) of one or more glycerol monoalkyl ether(s) of the generalformula

R—O—CH₂—CHOH—CH₂OH

[0023] in which R is a branched or unbranched C₃-C₁₈-alkyl group, wherethe alkyl group can be substituted by one or more hydroxyl and/orC₁-C₄-alkoxy group(s) and/or the alkyl chain can be interrupted by up tofour oxygen atoms, with

[0024] b) an antioxidant or two or more antioxidants as stabilizer(s).

[0025] In this connection, the simultaneous presence of phosphocholinesand/or phosphocholine derivatives, in particular alkylphosphocholines,in the compositions according to the invention is excluded.

[0026] The present invention relates in particular to the3-alkoxy-1,2-propanediols. The glycerol monoalkyl ethers according tothe invention can be present as racemate (D,L) or in the form ofenantiomer-enriched mixtures of the D- or L-form, or in the form of thepure enantiomers.

[0027] In one embodiment, the alkyl chain is interrupted by up to 4oxygen atoms, is therefore introduced by an alcohol group which isaccessible from an alcohol or diol by reaction with ethylene oxideand/or propylene oxide. In another embodiment, the alkyl group is ahydrocarbon group.

[0028] Here, the alkyl chain in the alkyl group R of the glycerolmonoalkyl ether can contain alkyleneoxy groups, such as, for example,ethyleneoxy and/or propyleneoxy groups.

[0029] The alkyl group preferably contains 6 to 12 carbon atoms,particularly preferably 6 to 10 carbon atoms, in particular 8 carbonatoms, e.g. a preferred alkyl group is a hydrocarbon group having 8carbon atoms, in particular a 2-ethylhexyl group. Thus, the particularlypreferred glycerol monoalkyl ether is3-[(2-ethylhexyl)oxy]-1,2-propanediol, which is marketed under the tradename Sensiva® SC 50 by Schulke & Mayr.

[0030] Antioxidants which act according to the invention as stabilizersfor the glycerol monoalkyl ethers are acetylcysteine,3-tert-butyl-4-hydroxyanisole, 2,6-di-tert-butyl-p-cresol,tert-butylhydroquinone, caffeic acid, chlorogenic acid, cysteine,cysteine hydrochloride, decylmercaptomethyl-imidazole,diamylhydroquinone, di-tert-butylhydro-quinone, dicetylthiodipropionate, digalloyl trioleate, dilauryl thiodipropionate,dimyristyl thiodipropionate, dioleyl tocopheryl methylsilanol, disodiumrutinyl disulphate, distearyl thiodipropionate, ditridecylthiodipropionate, dodecyl gallate, erythorbic acid, ethyl ferulate,ferulic acid, hydroquinone, p-hydroxyanisole, hydroxylaminehydrochloride, hydroxylamine sulphate, isooctyl thioglycolate, kojicacid, madecassicoside, methoxy-PEG-7-rutinyl succinate,nordihydroguaiaretic acid, octyl gallate, phenylthioglycolic acid,phloroglucinol, propyl gallate, rosmarinic acid, rutin, sodiumerythorbate, sodium thioglycolate, sorbityl furfural, thiodiglycol,thiodiglycolamide, thiodiglycolic acid, thioglycolic acid, thiolacticacid, thiosalicylic acid, tocophereth-5, tocophereth-10, tocophereth-12,tocophereth-18, tocophereth-50, tocophersolan, tocopherol (e.g. vitaminE) and its derivatives (e.g. vitamin E derivatives such as vitamin Eacetate, vitamin E linoleate, vitamin E nicotinate and vitamin Esuccinate), o-tolylbiguanide, tris(nonylphenyl) phosphite, dexpanthenol,alpha-hydroxycarboxylic acids (e.g. glycolic acid, lactic acid, mandelicacid) and salts thereof, p-hydroxybenzoic esters (e.g. methyl, ethyl,propyl or butyl esters thereof), dimethyloldimethylhydantoin,N-acylamino acids and salts thereof (e.g. N-octanoylglycine, LipacideC8G) and hinokitol. Of these, vitamin E and its derivatives,3-tert-butyl-4-hydroxyanisole and 2,6-di-tert-butyl-p-cresol arepreferred, and vitamin E and vitamin E acetate are more preferred.

[0031] In this connection, preference is given to antioxidants whichalready have a physiologically favourable action independently ofglycerol monoalkyl ethers, or display said action in—possiblysynergistic—combination with the glycerol monoalkyl ether.

[0032] The tocopherols are particularly effective antioxidants accordingto the invention (see the experiments in Table 1 of Example 1). Inaddition, the tocopherols are particularly desirable antioxidants withregard to the applications, which are associated with strict legalprovisions and toxicity tests, of the compositions comprising glycerolmonoalkyl ethers according to the invention in the preparation ofcosmetics and pharmaceuticals.

[0033] Tocopherols occur in plant oils, those being particularly rich intocopherols being seed oils from soya, wheat, maize, rice, cotton,lucerne and nuts, fruits and vegetables such as raspberries, legumes,fennel, paprika and celery.

[0034] The physiological action of tocopherols is based on theirproperties as free-radical scavengers. Thus, the tocopherols, if theyare used according to the invention as antioxidants and thus also passin small amounts into the preparations provided with glycerol alkylethers, can for their part act as physiologically active antioxidantseven in the cell membrane and in lipoproteins. Alpha-tocopherol (vitaminE, antisterility factor) is the most physiologically effective and mostwidespread natural tocopherol.

[0035] Although the tocopherols used may be of synthetic origin,tocopherols of natural origin can be used. It is possible to usesterically uniform enantiomers or enantiomer mixtures of tocopherols andaccordingly, for the derivatization to acetate, succinate, linoleate ornicotinate, it is possible to use tocopherols of natural and/orsynthetic origin and sterically uniform enantiomers or mixtures oftocopherols (in particular alpha-tocopherol).

[0036] Here, the compositions according to the invention, i.e. inparticular the concentrates and working solutions, are preferably freefrom ascorbic acid and its derivatives (see Experiments H, N, I and O inTable 1 in Example 1). In a further preferred embodiment of theinvention, the presence of sulphite, hydrogensulphite, disulphite and/ordisulphide is excluded.

[0037] The compositions according to the invention can also compriseadditives having an auxiliary and/or additive and/or active ingredientfunction. Such additives are, for example, water, alcohols, such asethanol, propanols, benzyl alcohol, phenylalkanols, polyols, such asethylene glycol, propylene glycol, glycerol, butanediols, pentanediols,silicone compounds, such as cyclomethicones, deodorant activeingredients, such as triclosan, farnesol, triethyl citrate, diglycerolcaprate, chitosan, monolaurin, aluminium salts, zirconium salts,fragrances, odour absorbers, surfactants, such as anionic surfactants,nonionic surfactants (e.g. alkyl polyglycosides), amphotericsurfactants, preservatives, antimicrobial active ingredients,dibromodicyanobutane, biocides, fungicides, virucides,antiinflammatories, emollients, moisturizers, refatting activeingredients, skincare substances, skin protection substances, perfumes,dyes, thickeners, buffers. Preferred additives which can be added to thecompositions according to the invention are water and/or alcohols and/orpolyols, in particular water, ethanol and propylene glycol, and mixturesthereof.

[0038] In a preferred embodiment, the antioxidant and its amount (inparticular its weight ratio to the glycerol monoalkyl ether) is chosensuch that, following storage of the composition at room temperature forone or two years, the Merckoquant® peroxide test registers a peroxidecontent of less than 5 ppm, more preferably even 0.5 or less ppm, ofH₂O₂. Examples of such antioxidants and compositions according to theinvention are given in Example 1, and compositions based thereon usingthe other said antioxidants can, if desired, be mixed. Alternatively,the antioxidant and the amount thereof can be chosen such that,following storage of the composition at room temperature for 6 months,the peroxide number is 1 or less than 1, and exemplary compositions aregiven in Example 2.

[0039] In this connection, the composition according to the invention ispreferably formulated with additive such that it does not contain abuffer or a buffer mixture, particularly when, as described later, it isin the form of a concentrate.

[0040] The compositions according to the invention are characterized bythe fact that the glycerol monoalkyl ether is stabilized bycomparatively small amounts of antioxidant. In this connection, theweight ratio (wt./wt.) of glycerol monoalkyl ether to antioxidant in thecomposition according to the invention (concentrate, working solution)is in the range from 50,000:1 to 1:20, preferably 20,000:1 to 1:5, morepreferably 10,000:1 to 1:2, e.g. 9995:5 or 1:1.8.

[0041] If the composition is in the form of a concentrate, then theconcentrate comprises 80 or more % by weight, preferably 90 or more % byweight, more preferably 95 or more % by weight, in particular 99 or more% by weight, of glycerol monoalkyl ether.

[0042] Such a concentrate can, for example, comprise from 95 to 99.999%by weight, preferably from 99 to 99.99% by weight, more preferably from99.5 to 99.95% by weight, e.g. 99.9% by weight or 99.95% by weight, ofglycerol monoalkyl ether.

[0043] Concentrates according to the invention are preferablyadditive-free or at least low-additive, i.e. they comprise 30% by weightor less, preferably 10% by weight or less, of additive, in particularanhydrous concentrates are preferred. Particular preference is given toconcentrates which consist only of glycerol monoalkyl ether andantioxidant, i.e. do not comprise additive.

[0044] In this connection, the weight ratio (wt./wt.) of glycerolmonoalkyl ether to antioxidant in the concentrate can be in the rangefrom 20,000:1 to 50:1, preferably 10,000:1 to 100:1, more preferably5000:1 to 500:1, e.g. 9995:5 or 999:1.

[0045] Exemplary concentrates according to the invention, which allcomprise the preferred 3-[(2-ethylhexyl)oxy]-1,2-propanediol, consist of99.5 to 99.95% by weight of this preferred glycerol monoalkyl ether and0.05 to 0.5% by weight of an antioxidant chosen from the groupconsisting of vitamin E and its derivatives,3-tert-butyl-4-hydroxyanisole and 2,6-di-tert-butyl-p-cresol, preferablyvitamin E and vitamin E acetate, and mixtures thereof, and consisting inparticular only of 3-[(2-ethylhexyl)oxy]-1,2-propanediol andantioxidant, i.e. they comprise none of said additives.

[0046] Particularly preferred concentrates according to the inventionare

[0047] a) 99.95% by weight of 3-[(2-ethylhexyl)oxy]-1,2-propanediol and0.05% by weight of antioxidant chosen from vitamin E and vitamin Ederivatives and mixtures thereof, and

[0048] b) 99.9% by weight of 3-[(2-ethylhexyl)oxy]-1,2-propanediol and0.1% by weight of antioxidant chosen from vitamin E and vitamin Ederivatives and mixtures thereof.

[0049] Compositions according to the invention, e.g. concentrates, may,for example, be characterized in that they have a pH of from 2 to 4,preferably 2.5 to 3.5, more preferably 2.8 to 3.2, e.g. 3.

[0050] On the other hand, the composition according to the invention canalso be in the form of a working solution. Such a working solutioncomprises 60% by weight or less, preferably 40% by weight or less, morepreferably 20% by weight or less, of glycerol monoalkyl ethers. Forexample, a concentrate according to the invention can be dissolved, i.e.diluted, in a suitable amount of an additive. It is also possible toprepare a working solution according to the invention by adding acorresponding amount of glycerol monoalkyl ether (e.g.3-[(2-ethylhexyl)oxy]-1,2-propanediol) and antioxidant in any order toone or more of the additives (e.g. water, alcohols and/or polyols). Inthis connection, the glycerol monoalkyl ether:antioxidant weight ratiocan be in the ratio ranges given above for the concentrates according tothe invention, e.g. when the working solution is obtained directly fromthe concentrate by dilution.

[0051] Alternatively, if desired, the optimum amount of antioxidant(e.g. the weight ratio of glycerol monoalkyl ether to antioxidant) can,in a specific application case, be determined by the person skilled inthe art by means of a few experiments or can arise directly from thedesired application. Thus, further possible weight ratios (wt./wt.) ofglycerol monoalkyl ether to antioxidant in the working solution are inthe range from 20:1 to 1:20, preferably 10:1 to 1:10, more preferably5:1 to 1:5, e.g. 2:1 or 1:2.

[0052] Preferred compositions have a pH of from 2 to 4, preferably 2.5to 3.5, more preferably 2.8 to 3.2, in particular 3. If the composition,e.g. as concentrate, is anhydrous, then this pH refers for this specificcomposition according to the invention to a 50% strength mixture of thecomposition with water, the pH of which is then determinedconventionally.

[0053] The compositions according to the invention, i.e. in particularthe concentrates and working solutions, can be added to cosmetic and/orpharmaceutical preparations, for example, as is correspondingly alreadyknown from the use of glycerol monoalkyl ethers from EP 0 599 433 A1 andDE 41 40 474 A1. Furthermore, it is also possible to use thecompositions according to the invention in technical products which areto be provided with glycerol monoalkyl ethers and in which peroxides areundesired, e.g. preparations comprising compounds which contain dyes orperfumes or which are unsaturated or sensitive to oxidation. Suchpreparations or technical products are, for example, deodorantpreparations, skincare preparations, sunscreen preparations, babyproducts, cosmetics for sensitive skin, cosmetic preparations, such asaftershaves, cosmetics based on or partially based on natural rawmaterials, stabilizers for cosmetic and/or pharmaceutical preparations,disinfectants for skin, hands and wounds, antiseptics, antimicrobialwashing lotions, compositions for hair treatment and antimicrobiallubricants. Particular preference is given to the use of theconcentrates and working solutions according to the invention indeodorant preparations and skincare preparations.

[0054] The addition or incorporation of the compositions according tothe invention, i.e. concentrates and working solutions, is usuallycarried out such that the corresponding cosmetic and/or pharmaceuticalpreparation is provided with 0.05 to 5% by weight, preferably 0.1 to 1%by weight, more preferably 0.2 to 0.6% by weight, e.g. 0.3% by weight or0.5% by weight, of glycerol monoalkyl ether.

[0055] The compositions, concentrates and working solutions according tothe invention, and the cosmetic and/or pharmaceutical preparations canbe in the form of solid, semisolid or liquid, gel-like or emulsion-likepreparations.

[0056] The compositions are prepared by simple mixing, e.g. the glycerolmonoalkyl ether (in particular Sensiva® SC 50) is initially introduced,the antioxidant (e.g. vitamin E or vitamin E derivatives, dissolved orpreferably as the pure substance) is dissolved with stirring and, whereappropriate, the additives are homogeneously stirred in.

[0057] According to the invention, it has surprisingly been found thatcompositions which comprise a combination of one or more glycerolmonoalkyl ethers with an antioxidant or two or more antioxidants asstabilizers are storable and stable for a few months to a few yearsunder practical conditions, i.e. at 0° C. to 40° C. The goodhandleability of concentrates according to the invention is particularlyadvantageous.

[0058] The invention offers the following advantages:

[0059]

The formation of peroxides, detectable by measuring the peroxide numberor using the Merckoquant® peroxide test analysis strips, can be avoidedor at least severely restricted.

[0060]

The content in stored compositions according to the invention, inparticular concentrates, of undesired degradation products of lowmolecular weight is significantly reduced.

[0061]

The neck-in effect can be avoided.

[0062]

The applications-related difficulties for pharmaceutical and/or cosmeticpreparations which it has hitherto not been possible to exclude whenusing glycerol monoalkyl ethers are avoided.

[0063]

Virtually no changes in odour occur during storage.

[0064]

The probability of incompatibilities with other cosmetic ingredients isreduced.

[0065] The invention described is able to utilize the full potential ofglycerol monoalkyl ethers for cosmetic and/or pharmaceuticalapplications.

[0066] The surprising effects which are achieved are illustrated by theexamples below.

EXAMPLES

[0067] In the examples below, the proportions in the mixtures are givenin % by weight.

[0068] The following terms are used in the examples below: BHT2,6-di-tert-butyl-p-cresol, obtainable from Fluka BHA 3-tert-butyl-4-hydroxyanisole, obtainable from Fluka Ascorbyl palmitate6-0-palmitoyl-L-ascorbic acid, obtainable from Fluka Sensiva ® SC 503-[(2-ethylhexyl)oxy]-1,2- propanediol Lipacide C8G N-octanoylglycine,obtainable from Seppic

[0069] The data in “ppm of H₂O₂” refer to the peroxide determinationusing Merckoquant® peroxide test analysis strips. This semiquantitativemethod for determining peroxide was carried out as follows:

[0070] About 0.5 g of the sample to be investigated is placed in a testtube and treated with the same amount of demineralized water. The twophases are mixed by shaking, and a Merckoquant® peroxide test analysisstrip is dipped in for one second. The damp strip is removed from theliquid and the peroxide content is read off after 15 seconds using thereference scale and noted. If the peroxide content is too high, theamount is doubled with demineralized water, again shaken etc., until areading is possible using the reference scale. The value obtained isback-calculated using the dilution.

[0071] The peroxide number (PON) gives the amount of peroxide inmilliequivalents of active oxygen which is present in 1000 g ofsubstance, determined in accordance with the method below.

[0072] 5.00 g of substance are weighed into a 250 ml Erlenmeyer flaskwith ground-glass stopper and dissolved in 30 ml of a mixture of 2 partsby volume of chloroform R and 3 parts by volume of acetic acid 98% Rwith shaking. Following the addition of 0.5 ml of saturated potassiumiodide solution R, the solution is shaken for exactly 1 minute, thentreated with 30 ml of water and slowly titrated with 0.01 N sodiumthiosulphate solution with continuous shaking until the yellowcoloration has virtually disappeared. Following the addition of 5 ml ofstarch solution R, the titration is continued with vigorous shakinguntil the blue coloration disappears (n₁ ml of 0.01 N sodiumthiosulphate solution). A control experiment is carried out under thesame conditions (n₂ ml of 0.01 N sodium thiosulphate solution). Forthis, at most 0.1 ml of 0.01 N sodium thiosulphate solution must beconsumed.

[0073] The peroxide number is calculated as follows:${PON} = \frac{10\left( {n_{1} - n_{2}} \right)}{m}$

[0074] where m is the initial weight of the substance in grams.

[0075] The method is explained in more detail in DAB 9-Kommentar [GermanPharmacopoeia 9—Commentary] (K. Hartke, E. Mutschler, Editor,Wissenschaftliche Verlagsgesellschaft mbH Stuttgart, 9th edition 1986).

Example 1

[0076] 3-[(2-ethylhexyl)oxy]-1,2-propanediol was mixed with a variety ofsubstances, and the stability of the compositions during storage at roomtemperature in blue polyethylene bottles was tested (sample A (Alu) wasstored in an aluminium container). Following preparation of the samples,the value for ppm of H₂O₂ and the pH were determined at regularintervals.

[0077] The pH of the anhydrous solutions is given as the value which a50% strength slurry of the respective anhydrous solution indemineralized water has, determined using Merck® pH indicator strips.

[0078] The results of the individual experiments are given in Table 1.In this connection, information such as, for example, “2-5” for the ppmof H₂O₂ value means that the value on the reference scale is between twovalues, for example between 2 and 5. TABLE 1 A(Alu) A B C D E F G BHT0.10 0.05 0.10 BHA 0.05 Vitamin E, Fluka 0.10 0.05 Sensiva ® SC 50100.00 100.00 99.90 99.95 99.90 99.95 99.90 99.95 PON S. 0.5 0.5 0.5 0.50.5 0.5 0.5 0.5 ppm of H₂O₂ 7 d. 0.5 2 0.5 0.5 0.5 0.5 0.5 0.5 pH 7 d. 33 3 3 3 3 3 3 ppm of H₂O₂ 9 d. 0.5-1 2 0.5 0.5 0.5 0.5 0.5 0.5 pH 9 d. 33 3 3 3 3 3 3 ppm of H₂O₂ 2 w. 2 2-5 0.5 0.5 0.5 0.5 0.5 0.5 pH 2 w. 3 33 3 3 3 3 3 ppm of H₂O₂ 3 w. 2-5 2-5 0.5 0.5 0.5 0.5 0.5 0.5 pH 3 w. 3 33 3 3 3 3 3 ppm of H₂O₂ 4 w. 2-5 2-5 0.5 0.5 0.5 0.5 0.5 0.5 pH 4 w. 3 33 3 3 3 3 3 ppm of H₂O₂ 5 w. 2-5 2-5 0.5 0.5 0.5 0.5 0.5 0.5 pH 5 w. 3 33 3 3 3 3 3 ppm of H₂O₂ 6 w. 2-5 2-5 0.5 0.5 0.5 0.5 0.5 0.5 pH 6 w. 3 33 3 3 3 3 3 ppm of H₂O₂ 7 w. 5 2-5 0.5 0.5 0.5 0.5 0.5 0.5 pH 7 w. 3 3 33 3 3 3 3 ppm of H₂O₂ 8 w. 5 2-5 0.5 0.5 0.5 0.5 0.5 0.5 pH 8 w. 3 3 3 33 3 3 3 Hazen colour number 8 w. <5 <5 <5 <5 ppm of H₂O₂ 2 m. 25 2-5 0.50.5 0.5 0.5 0.5 0.5 pH 2 m. 3 3 3 3 3 3 3 3 ppm of H₂O₂ 3 m. 25-50 2-50.5 0.5 0.5 0.5 0.5 0.5 ppm of H₂O₂ 4 m. 25-50 5 0.5 0.5 0.5 0.5 0.5 0.5ppm of H₂O₂ 5 m. 50 5 0.5 0.5 0.5 0.5 0.5 0.5 ppm of H₂O₂ 6.5 m. 50 50.5 0.5 0.5 0.5 0.5 0.5 ppm of H₂O₂ 8.5 m. 25-50 5 0.5 0.5 0.5 0.5 0.50.5 ppm of H₂O₂ 11 m 10-25 10 0.5 0.5 0.5 0.5 0.5 0.5 ppm of H₂O₂ 1 y.10 10 0.5 0.5 0.5 0.5 0.5 0.5 ppm of H₂O₂ 14 m. 10 10 0.5 0.5 0.5 0.50.5 0.5 ppm of H₂O₂ 16 m. 10 10 0 0 0 0 0 0 ppm of H₂O₂ 2 y. 0 10-25 00.5 0 0 0 0 Appearance of the bottle 2 y. n.c. neck in n.c. n.c. n.c.nc. n.c. nc. PON 2 y. 11 m. 25.3 0.2 0.4 n.d. n.d. Appearance of thebottle 11 m. n.c. consider- n.c. nc. n.c. n.c. n.c. n.c. 2 y. able neckin H I J K L M N O BHT 0.05 0.025 BHA 0.05 0.025 Vitamin E, Fluka 0.050.025 Ascorbyl palmitate 0.10 0.05 0.05 0.025 Dexpanthenol 0.10 0.05Sensiva ® SC 50 99.90 99.95 99.90 99.95 99.90 99.95 99.90 99.95 PON S.0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 ppm of H₂O₂ 7 d. 0.5 0.5 0.5-2 0.5-2 0.50.5 0.5 0.5 pH 7 d. 3 3 3 3 3 3 3 3 ppm of H₂O₂ 9 d. 0.5 0.5 2 2 0.5 0.50.5 0.5 pH 9 d. 3 3 3 3 3 3 3 3 ppm of H₂O₂ 2 w. 0.5-2 0.5-2 2 3 0.5 0.50.5 0.5 pH 2 w. 3 3 3 3 3 3 3 3 ppm of H₂O₂ 3 w. 2-5 2 2-5 2-5 0.5 0.50.5-2 0.5-2 pH 3 w 3 3 3 3 3 3 3 3 ppm of H₂O₂ 4 w. 2-5 2-5 2-5 2-5 0.50.5 0.5-2 0.5-2 pH 4 w. 3 3 3 3 3 3 3 3 ppm of H₂O₂ 5 w. 2-5 2-5 2-5 2-50.5 0.5 2 2 pH 5 w. 3 3 3 3 3 3 3 3 ppm of H₂O₂ 6 w. 10 5 2-5 2-5 0.50.5 2 2 pH 6 w. 3 3 3 3 3 3 3 3 ppm of H₂O₂ 7 w. 10 5 2-5 2-5 0.5 0.52-5 2 pH 7 w 3 3 3 3 3 3 3 3 ppm of H₂O₂ 8 w. 25 10 2-5 2-5 0.5 0.5 2-52 pH 8 w. 3 3 3 3 3 3 3 3 Hazen colour number 8 w. <5 <5 <5 <5 ppm ofH₂O₂ 2 m. 25 10-25 2-5 2-5 0.5 0.5 2-5 2 pH 2 m. 3 3 3 3 3 3 3 3 ppm ofH₂O₂ 3 m. 25-50 25 2-5 2-5 0.5 0.5 5 5 ppm of H₂O₂ 4 m. 50 25-50 2-5 2-50.5 0.5 5 5 ppm of H₂O₂ 5 m. 50-100 50 5 5 0.5 0.5 5-10 5 ppm of H₂O₂6.5 m. 100 50 5 5 0.5 0.5 10 5 ppm of H₂O₂ 8.5 m. 100-200 100 5 5 0.50.5 10 5 ppm of H₂O₂ 11 m. 200 100 5 5 0.5 0.5 10 5 ppm of H₂O₂ 1 y. 200100 5 5 0.5 0.5 10 5 ppm of H₂O₂ 14 m. 100 160 5 5 0.5 0.5 5 2 ppm ofH₂O₂ 16 m. 100 100 5 5-10 0 0 5 5 ppm of H₂O₂ 2 y. 10-25 25 5 5 0 0 2-52-5 Appearance of the bottle 2 y. neck in neck in n.c. n.c. n.c. nc.n.c. nc. PON 2 y. 11 m. 19.5 Appearance of the bottle 11 m. consider-consider- n.c. nc. n.c. n.c. n.c. nc. 2 y. able able neck in neck in

[0079] The experiments listed in Table 1 thus demonstrate that BHT, BHA,vitamin E and dexpanthenol stabilize the glycerol monoalkyl ethers overa long period, and in particular that the appearance of peroxides,determined by the Merckoquant® peroxide test, is avoided and as a resultthe neck-in effect is no longer observed when said antioxidants areused. The pH of the samples, as shown by reference to the measurementafter 2 months, remains unchanged.

[0080] It is notable that according to the invention even 0.05% byweight of the antioxidants BHT, BHA, vitamin E and dexpanthenol, whichare used by way of example, exhibit the stabilizing effect.

[0081] By contrast, ascorbyl palmitate does not stabilize the glycerolmonoalkyl ethers (see Experiments H and I) or inhibit its stabilizationby vitamin E (see Experiments N and O), the lack of stabilizing effect,or destabilization, being significantly marked after storage for just 8weeks. Accordingly, the compositions according to the invention(concentrates, working solutions) are preferably free from ascorbic acidor ascorbic acid derivatives and salts.

Example 2

[0082] The peroxide number of compositions of Sensiva® SC 50 andLipacide C8G salts was compared with the stability of mixtures ofSensiva® SC 50 and other salts. The results of individual experimentswith a sample of Sensiva® SC 50, which already has a low content ofperoxide, are given in Table 2. TABLE 2 A B C D E 20% strength aqueous90  3 solution of Lipacide C8G as Na salt 15% strength aqueous  3solution of Na citrate 15% strength aqueous  3 Na sulphate solutionSensiva ® SC 50 100  10 97 97 97 Appearance S. cl c cl c cl c cl c notdissolved, filtered PON S. 10 10 10 10 10 PON  4 d. 10 0.5 10 10 10 PON 9 d. 10-25 0 10 25 25 PON  6 w. 25 0 10 25 25 PON 11 w. 25 0 10 25 25PON  6 m. 20 0  1  5 10 PON  2 y. 2 m.  5-10  0  0 2-5 2-5 PE bottle  2y. 2 m. considerable n.c. nc. neck in neck in neck in Appearance cl c clyl cl yl kr c cl c Hazen colour number  0 62 43  2  0

[0083] Result:

[0084] In the presence of Lipacide C8G sodium salts, the peroxide numberdecreases as a function of time, and at the same time the neck-in effectis avoided. This effect could not be achieved using sodium sulphate andsodium citrate solutions.

1. Composition characterized in that it comprises a combination a) ofone or more glycerol monoalkyl ether(s) of the general formulaR—O—CH₂—CHOH—CH₂OH in which R is a branched or unbranched C₃-C₁₈-alkylgroup, where the alkyl group can be substituted by one or more hydroxyland/or C₁-C₄-alkoxy group(s) and/or the alkyl chain can be interruptedby up to four oxygen atoms, with b) an antioxidant or two or moreantioxidants chosen from the group consisting of acetylcysteine,3-tert-butyl-4-hydroxyanisole, 2,6-di-tert-butyl-p-cresol,tert-butylhydroquinone, caffeic acid, chlorogenic acid, cysteine,cysteine hydrochloride, decylmercaptomethylimidazole,diamylhydroquinone, di-tert-butylhydroquinone, dicetyl thiodipropionate,digalloyl trioleate, dilauryl thiodipropionate, dimyristylthiodipropionate, dioleyl tocopheryl methylsilanol, disodium rutinyldisulphate, distearyl thiodipropionate, ditridecyl thiodipropionate,dodecyl gallate, erythorbic acid, ethyl ferulate, ferulic acid,hydroquinone, p-hydroxyanisole, hydroxylamine hydrochloride,hydroxylamine sulphate, isooctyl thioglycolate, kojic acid,madecassicoside, methoxy-PEG-7-rutinyl succinate, nordihydroguaiareticacid, octyl gallate, phenylthioglycolic acid, phloroglucinol, propylgallate, rosmarinic acid, rutin, sodium erythorbate, sodiumthioglycolate, sorbityl furfural, thiodiglycol, thiodiglycolamide,thiodiglycolic acid, thioglycolic acid, thiolactic acid, thiosalicylicacid, tocophereth-5, tocophereth-10, tocophereth-12, tocophereth-18,tocophereth-50, tocophersolan, tocopherol (in particular vitamin E) andits derivatives (in particular vitamin E derivatives such as vitamin Eacetate, vitamin E linoleate, vitamin E nicotinate and vitamin Esuccinate), o-tolylbiguanide, tris(nonylphenyl) phosphite, dexpanthenol,alpha-hydroxycarboxylic acids (in particular glycolic acid, lactic acid,mandelic acid) and salts thereof, p-hydroxybenzoic esters (in particularmethyl, ethyl, propyl or butyl esters thereof),dimethyloldimethylhydantoin, N-acylamino acids and salts thereof (inparticular N-octanoylglycine) and hinokitol as stabilizer(s), thesimultaneous presence of phosphocholines and phosphocholine derivativesbeing excluded.
 2. Composition according to claim 1, characterized inthat the alkyl group R contains 6 to 12 carbon atoms, preferably 6 to 10carbon atoms, in particular 8 carbon atoms.
 3. Composition according toclaim 2, characterized in that the alkyl group R is 2-ethylhexyl. 4.Composition according to one of claims 1 to 3, characterized in that theantioxidant is chosen from vitamin E and its derivatives,3-tert-butyl-4-hydroxyanisole and 2,6-di-tert-butyl-p-cresol, preferablyvitamin E and vitamin E acetate.
 5. Composition according to one ofclaims 1 to 4, characterized in that it comprises one or more furtheradditives having an auxiliary and/or additive and/or active ingredientfunction.
 6. Composition according to one of claims 1 to 5,characterized in that the peroxide number is 1 or less than
 1. 7.Composition according to one of claims 1 to 6, characterized in that itdoes not comprise a buffer or a buffer mixture.
 8. Composition accordingto one of claims 1 to 7 in the form of a concentrate, characterized inthat the concentrate comprises 80 or more % by weight, preferably 90 ormore % by weight, more preferably 95 or more % by weight, of glycerolmonoalkyl ether.
 9. Concentrate according to claim 8, characterized inthat the weight ratio (wt./wt.) of glycerol monoalkyl ether toantioxidant is in the range from 20,000:1 to 50:1, preferably 10,000:1to 100:1, more preferably 5000:1 to 500:1, in particular 9995:5 or999:1.
 10. Concentrate according to claim 8 or 9, characterized in thatit comprises from 95 to 99.999% by weight, preferably from 99 to 99.99%by weight, more preferably from 99.5 to 99.95% by weight, in particular99.9% by weight or 99.95% by weight, of glycerol monoalkyl ether, andthe remainder is antioxidant.
 11. Concentrate characterized in that itcomprises a) from 99.5 to 99.95% by weight of3-[(2-ethylhexyl)oxy]-1,2-propanediol and b) 0.05 to 0.5% by weight ofan antioxidant chosen from the group consisting of vitamin E and itsderivatives, 3-tert-butyl-4-hydroxyanisole and2,6-di-tert-butyl-p-cresol, preferably vitamin E and vitamin E acetate,and mixtures thereof.
 12. Concentrate according to claim 11,characterized in that it comprises 99.9% by weight of3-[(2-ethylhexyl)oxy]-1,2-propanediol and 0.1% by weight of antioxidantchosen from vitamin E and its derivatives, and mixtures thereof. 13.Concentrate according to claim 11, characterized in that it comprises99.95% by weight of 3-[(2-ethylhexyl)oxy]-1,2-propanediol and 0.05% byweight of antioxidant chosen from vitamin E and vitamin E derivatives,and mixtures thereof.
 14. Concentrate according to one of claims 9 to13, characterized in that it has a pH of 2 to 4, preferably 2.5 to 3.5,more preferably 2.8 to 3.2, in particular
 3. 15. Composition accordingto one of claims 1 to 8 in the form of a working solution, characterizedin that the working solution comprises 60% by weight or less, preferably40% by weight or less, more preferably 20% by weight or less, ofglycerol monoalkyl ether.
 16. Use of a composition, in particular of aconcentrate or of a working solution, according to one of claims 1 to 15in cosmetic and/or pharmaceutical preparations.
 17. Use according toclaim 16, characterized in that the cosmetic and/or pharmaceuticalpreparation comprises from 0.05 to 5% by weight, preferably 0.1 to 1% byweight, preferably 0.2 to 0.6% by weight, in particular 0.3% by weight,of glycerol monoalkyl ether, preferably3-[(2-ethylhexyl)oxy]-1,2-propanediol.
 18. Use of an antioxidant chosenfrom the group consisting of acetylcysteine,3-tert-butyl-4-hydroxyanisole, 2,6-di-tert-butyl-p-cresol,tert-butylhydroquinone, caffeic acid, chlorogenic acid, cysteine,cysteine hydrochloride, decylmercaptomethylimidazole,diamylhydroquinone, di-tert-butylhydroquinone, dicetyl thiodipropionate,digalloyl trioleate, dilauryl thiodipropionate, dimyristylthiodipropionate, dioleyl tocopheryl methylsilanol, disodium rutinyldisulphate, distearyl thiodipropionate, ditridecyl thiodipropionate,dodecyl gallate, erythorbic acid, ethyl ferulate, ferulic acid,hydroquinone, p-hydroxyanisole, hydroxylamine hydrochloride,hydroxylamine sulphate, isooctyl thioglycolate, kojic acid,madecassicoside, methoxy-PEG-7-rutinyl succinate, nordihydroguaiareticacid, octyl gallate, phenylthioglycolic acid, phloroglucinol, propylgallate, rosmarinic acid, rutin, sodium erythorbate, sodiumthioglycolate, sorbityl furfural, thiodiglycol, thiodiglycolamide,thiodiglycolic acid, thioglycolic acid, thiolactic acid, thiosalicylicacid, tocophereth-5, tocophereth-10, tocophereth-12, tocophereth-18,tocophereth-50, tocophersolan, tocopherol (in particular vitamin E) andits derivatives (in particular vitamin E derivatives such as vitamin Eacetate, vitamin E linoleate, vitamin E nicotinate and vitamin Esuccinate), o-tolylbiguanide, tris(nonylphenyl) phosphite, dexpanthenol,alpha-hydroxycarboxylic acids (in particular glycolic acid, lactic acid,mandelic acid) and salts thereof, p-hydroxybenzoic esters (in particularmethyl, ethyl, propyl or butyl esters thereof),dimethyloldimethylhydantoin, N-acylamino acids and salts thereof (inparticular N-octanoylglycine) and hinokitol, and mixtures thereof forthe long-term stabilization of a glycerol monoalkyl ether of the generalformula R—O—CH₂—CHOH—CH₂OH in which R is a branched or unbranchedC₃-C₁₈-alkyl group, where the alkyl group can be substituted by one ormore hydroxyl and/or C₁-C₄-alkoxy group(s) and/or the alkyl chain can beinterrupted by up to four oxygen atoms.
 19. Use according to claim 18,characterized in that the alkyl group R contains 6 to 12 carbon atoms,preferably 6 to 10 carbon atoms, in particular 8 carbon atoms.
 20. Useaccording to claim 19, characterized in that the alkyl group R is2-ethylhexyl.
 21. Use according to one of claims 18 to 20, characterizedin that the antioxidant is chosen from vitamin E and its derivatives,3-tert-butyl-4-hydroxyanisole and 2,6-di-tert-butyl-p-cresol, preferablyvitamin E and vitamin E acetate.
 22. Use according to one of claims 18to 21, characterized in that the weight ratio (wt./wt.) of glycerolmonoalkyl ether to antioxidant is in the range from 50,000:1 to 1:20,preferably 20,000:1 to 1:5, more preferably 10,000:1 to 1:2, inparticular 9995:1 or 1:1.8.
 23. Use according to one of claims 18 to 22,characterized in that one more further additives having an auxiliaryand/or additive and/or active ingredient function are present in thecombination.